The purpose of this work is to study physiological and pathological aspects of the renin-angiotensin system, with emphasis on the regulation of aldosterone secretion. Specific topics include the regulation of adrenal sensitivity to angiotensin II (AII) during altered sodium intake, and mechanisms of acti-vation of the steroidogenesis in the adrenal glomerulosa cell. Angiotensin II is the mediator of the aldosterone responses and adrenotrophic effects of sodium restriction. During sodium deprivation, AII-induced increases in adrenal glomerulosa AII receptors and 18-hydroxylase activity largely contribute to the increased sensitivity of the adrenal to AII. These studies have shown that the effectiveness of angiotensin II to induce such changes in the adrenal glomerulosa is also dependent on the sodium status, being reduced during sodium loading. The decreased adrenal sensitivity to angiotensin II during high sodium intake was restored to normal by administration of the dopamine antagonist metoclopramide, indicating that the adrenal action of angiotensin II can be modulated by dopaminergic inhibition. The peptide somatostatin, which has been shown to inhibit AII-stimulated aldosterone in rat adrenal glomerulosa cells, may be involved in the regulation of adrenal sensitivity to AII in this species, but not in dog, monkey or human, in which no somatostatin receptors are present in the adrenal glomerulosa zone. Hypophysectomy in the rat did not alter the ability of sodium restriction to increase adrenal glomerulosa AII receptors and 18-hydroxylase activity, but the pituitary gland was shown to be necessary to maintain the activity of the enzymes of the early aldosterone biosynthetic pathway. Studies using selective calmodulin antagonists in dispersed glomerulosa cells indicated that the steroidogenic action of AII is highly dependent on Ca-calmodulin mediated processes, while the action of ACTH is only partially cal-modulin-dependent. Other studies have been initiated on the characterization and regulation of angiotensin II receptors in specific areas of the brain involved in circulatory homeostasis.